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The role of IL‐12 in the control of MCMV is fundamentally different in mice with a retroviral immunodeficiency syndrome (MAIDS)
Author(s) -
Peacock Craig D,
Price Patricia
Publication year - 1999
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.1999.00810.x
Subject(s) - cytotoxic t cell , spleen , immunology , biology , virology , cytomegalovirus , phenotype , virus , herpesviridae , in vitro , viral disease , genetics , gene
The present study investigates the susceptibility of C57BL mice exhibiting T cell immunodeficiency and lymphadenopathy induced by LP‐BM5 murine leukaemia virus (MAIDS) to murine cytomegalovirus (MCMV). Treatment of normal (M–) mice with anti‐IL‐12 increased the contribution of IgG 1 to the hypergammaglobulinaemia induced by MCMV, consistent with a shift towards a Th2 phenotype. This impaired control of early MCMV replication in the liver, with little effect in the spleen. Control of hepatic infection correlated with a vigorous splenic NK cytotoxic response in a subgroup of IL‐12‐depleted M– mice that remained healthy, while others became moribund. Mortality in IL‐12‐depleted MAIDS (M+) mice given MCMV was ultimately greater than in M– controls, but was delayed despite high levels of MCMV in the liver. IL‐12 was required for optimal control of MCMV replication in M+ mice. This may involve cytotoxic activity because similar levels of infection were seen in bg/bg M+ mice, where the beige mutation impairs the formation of cytotoxic granules. Hence the ability of M+ mice to tolerate high titres of MCMV during acute infection may enable innate cytotoxic responses to clear MCMV. Interleukin‐12 depletion of M– mice also increased salivary gland MCMV titres and depressed delayed‐type hypersensitivity responses to MCMV antigen, normally mediated by CD4 + T cells. These changes were not observed in IL‐12‐depleted M+ mice.